Study Finds Increased GI Cancer Risk Among Individuals With Overweight, Obese BMIs Throughout Adulthood

Gastrointestinal (GI) cancers have been strongly associated with obesity, likely due to the chronic and persistent inflammation associated with obesity. Chronic inflammation has been linked to an increased risk of several GI cancers (e.g., pancreatic [pancreatitis], esophageal [esophagitis and Barrett esophagus], and colorectal [ulcerative colitis and Crohn disease]).

A retrospective cohort study published in JAMA Network Open examined the association between body mass index (BMI) at early, middle, and later adulthood, with GI cancer risk (colorectal cancer [CRC] and noncolorectal GI cancer), as well as the association between changing BMI and GI cancer risk. Additionally, the association between aspirin use and GI cancer risk was evaluated.

“In a population with significantly increasing rates of individuals with overweight or obesity, understanding the association of obesity with long-term disease risk, such as cancer, is necessary to improve public health…Inflammation can be ascribed to several means, including chronic infection or conditions that result in enhanced proinflammatory signaling, such as obesity,” the study authors wrote. “However, many questions remain regarding the impact of heightened baseline inflammation attributed to obesity on cancer risk, such as the effect of obesity or weight gain in early life on later cancer risk or how changing BMI over time alters cancer risk.”

A total of 135,161 participants aged 55 to 74 years across 10 screening centers were enrolled and randomized into 1 of 2 groups: the intervention (screening) group or the control group. Those in the intervention group received screenings for prostate, lung, colorectal, and ovarian cancers, whereas those in the control group received standard medical care. Through a baseline questionnaire (BQ) and a supplemental questionnaire (SQ), each participant recorded their BMI at 20 years of age (early adulthood), 50 years of age, (middle adulthood), and 55 years of age and older, or at the time of the study (later adulthood). Further, participants were asked to report how frequently they use aspirin, and those who reported using it 3 or more times per week were included in the final analysis.

Participants were excluded from the trial if they were younger than 55 years of age at the time of randomization; had a history of prostate, lung, colorectal, or ovarian cancers; prior surgical removal of the colon; treatment for cancer other than basal or squamous cell carcinoma of the skin; participated in another cancer screening or cancer primary prevention trial; or if they received a colonoscopy, sigmoidoscopy, or barium enema within 3 years prior to enrollment.

The mean (SD) follow-up of the examined cohorts was 13.9 (6.0) years, and the median follow-up was 14.9 (range, 0-24.2) years. During follow-up, 34,946 participants (25.9%) were diagnosed with cancer, of which 5088 (14.6%) were GI cancers (2803 [55.1%] CRC; 376 [7.4%] esophageal cancers; 485 [9.5%] gastric cancers; 348 [6.8%] liver cancers; and 1076 [21.1%] pancreatic cancers).

“Individuals with obesity are at higher risk of several conditions, including cancer. Interestingly, not all cancers are significantly associated with obesity; rather, it is more limited to those where cancer cells grow near adipose cells, potentially due to the impact of adipose cells on tumorigenesis,” the study authors wrote.

Study results indicated an increased GI cancer risk among participants with overweight (early adulthood: hazard ratio [HR], 1.17; 95% CI, 1.08-1.27; middle adulthood: HR, 1.18; 95% CI, 1.11-1.26; later adulthood: HR, 1.17; 95% CI, 1.09-1.25) and obese (early adulthood: HR, 1.31; 95% CI, 1.08-1.59; middle adulthood: HR, 1.50; 95% CI, 1.37-1.64; later adulthood: HR, 1.38; 95% CI, 1.27-1.49) BMI at different ages. Similarly, an increased risk of noncolorectal GI cancer was associated with an obese BMI in early (HR, 1.37; 95% CI, 1.04-1.80), middle (HR, 1.44; 95% CI, 1.27-1.65), and late (HR, 1.36; 95% CI, 1.21-1.53) adulthood, and an overweight BMI in middle (HR, 1.13; 95% CI, 1.03-1.24) and late (HR, 1.13; 95% CI, 1.03-1.24) adulthood. In addition, obese BMI in middle adulthood (HR, 1.55; 95% CI, 1.38-1.75) and later adulthood (HR, 1.39; 95% CI, 1.25-1.54) was associated with an increased risk of CRC.

The increase in BMI over time was associated with a higher risk of CRC (early adulthood: HR, 1.23; 95% CI, 1.10-1.37; middle adulthood: HR, 1.23; 95% CI, 1.13-1.34; later adulthood: HR, 1.39; 95% CI, 1.25-1.54) and noncolorectal GI cancers. Further, the use of aspirin 3 or more times per week did not significantly influence this association; however, it may not be effective in preventing GI cancers for those with overweight or obese BMIs.

“Our results indicate that individuals with overweight and obese BMIs had an increased risk of CRC and noncolorectal GI cancer with aspirin use 3 or more times per week, suggesting that aspirin may not be efficacious for prevention in overweight or obese states,” the authors wrote in the study. “…A suggestion may be that individuals with obesity need to increase aspirin frequency or dosage; however, increased aspirin use comes with its own risks, such as gastrointestinal bleeding.”

Individuals who had overweight or obese BMI in early and later adulthood (HR, 1.45; 95% CI, 1.28-1.64; P < .001) and those who moved from either underweight or normal BMI in early adulthood to overweight or obese BMI in later adulthood (HR, 1.23; 95% CI, 1.13-1.34; P < .001) had an increased risk of CRC. Similar connections were found with noncolorectal GI cancer risk without change in overweight or obese BMI (HR, 1.29; 95% CI, 1.13-1.47; P < .001) and underweight or normal to overweight or obese BMI (HR, 1.17; 95% CI, 1.06-1.29; P = .002).

When examining BMI from middle to later adulthood, investigators found that consistent overweight or obese BMI (HR, 1.37; 95% CI, 1.25-1.51; P < .001), changing from overweight or obese to underweight or normal BMI (HR, 1.47; 95% CI, 1.21-1.78; P < .001), and changing from underweight or normal to overweight or obese BMI (HR, 1.20; 95% CI, 1.06-1.34; P = .003) were associated with increased risk of CRC. This suggests that changes in BMI over time may influence the risk of GI cancer, according to the study authors.

Study limitations include the participants’ self-reporting of their height and weight used to calculate BMI on the BQ and SQ; aspirin dosing information was not collected in the BQ and was not accounted for in the analysis; the inability to correlate changes in BMI with aspirin use; and aspirin use being reported during the past year, whereas BMI could have changed before the questionnaires. Additionally, the current analysis only evaluated the association between the 2 factors, rather than the causation.

There is a possibility that all confounders were not accounted for in the multivariable logistic regression models. Further, the current study is a secondary analysis of a completed cancer screening trial, therefore, the information on exposure and outcome that was collected was not included in the original study.

“The results of the current study prompt further exploration into the mechanistic role of obese BMI in carcinogenesis…future research must focus on identifying cancer prevention mechanisms for this high-risk group,” the study authors wrote.

Reference

Loomans-Kropp H, Umar A. Analysis of Body Mass Index in Early and Middle Adulthood and Estimated Risk of Gastrointestinal Cancer. JAMA Netw Open. 2023;6(5):e2310002. doi:10.1001/jamanetworkopen.2023.10002